Genetic and clinical determinants of abdominal aortic diameter: genome-wide association studies, exome array data and Mendelian randomization study-Reference-Cited by-同舟云学术

Genetic and clinical determinants of abdominal aortic diameter: genome-wide association studies, exome array data and Mendelian randomization study

Published:2022-03-02 Issue:20 Volume:31 Page:3566-3579
ISSN:0964-6906
Container-title:Human Molecular Genetics
language:en
Short-container-title:

Author:

Portilla-Fernandez Eliana¹²^ORCID,Klarin Derek³⁴⁵,Hwang Shih-Jen⁶⁷,Biggs Mary L⁸⁹,Bis Joshua C⁸,Weiss Stefan¹⁰¹¹^ORCID,Rospleszcz Susanne¹²^ORCID,Natarajan Pradeep³⁴¹³¹⁴,Hoffmann Udo¹⁵,Rogers Ian S¹⁶,Truong Quynh A¹⁷,Völker Uwe¹⁰¹¹,Dörr Marcus¹⁸¹¹,Bülow Robin¹⁹,Criqui Michael H²⁰,Allison Matthew²⁰,Ganesh Santhi K²¹,Yao Jie²²,Waldenberger Melanie¹¹²³,Bamberg Fabian²⁴,Rice Kenneth M⁹,Essers Jeroen²⁵²⁶²⁷,Kapteijn Daniek M C²⁸,van der Laan Sander W²⁹^ORCID,de Knegt Rob J³⁰,Ghanbari Mohsen¹,Felix Janine F¹,Ikram M Arfan¹,Kavousi Maryam¹,Uitterlinden Andre G³¹,Roks Anton J M²,Danser A H Jan²,Tsao Philip S³²³³,Damrauer Scott M³⁴³⁵,Guo Xiuqing²²,Rotter Jerome I²²,Psaty Bruce M⁸³⁶³⁷,Kathiresan Sekar³⁴,Völzke Henry¹¹³⁸,Peters Annette¹²³⁹⁴⁰,Johnson Craig⁴¹,Strauch Konstantin⁴²⁴³⁴⁴,Meitinger Thomas¹¹⁴⁵⁴⁶,O’Donnell Christopher J¹⁴⁴⁷,Dehghan Abbas⁴⁸⁴⁹,

Affiliation:

1. Department of Epidemiology , Erasmus University Medical Center, Rotterdam, The Netherlands

2. Department of Internal Medicine , Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Rotterdam, The Netherlands

3. Center for Genomic Medicine , Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

4. Program in Medical and Population Genetics , Broad Institute of MIT and Harvard, Cambridge, MA, USA

5. Department of Surgery , Massachusetts General Hospital, Boston, MA, USA

6. Population Sciences Branch , Division of Intramural Research, NHLBI/NIH, Bethesda MD, USA

7. National Heart Lung and Blood Institute's Intramural Research Program's Framingham Heart Study , Framingham, MA, USA

8. Cardiovascular Health Research Unit , Department of Medicine, University of Washington, Seattle, WA, USA

9. Department of Biostatistics , University of Washington, Seattle, WA, USA

10. Department of Functional Genomics , Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany

11. DZHK (German Centre for Cardiovascular Research) , Partner Site Greifswald, Greifswald, Germany

12. Institute of Epidemiology , Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany

13. Cardiovascular Research Center , Massachusetts General Hospital, Boston, MA, USA

14. Department of Medicine , Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

15. Department of Radiology , Massachusetts General Hospital, Boston, MA, USA

16. Division of Cardiovascular Medicine , Stanford University, Stanford, CA, USA

17. Department of Radiology , Weill Cornell Medicine, New York, NY, USA

18. Department of Internal Medicine , University Medicine Greifswald, Greifswald, Germany

19. Department of Diagnostic Radiology and Neuroradiology , University Medicine Greifswald, Greifswald, Germany

20. Department of Family Medicine , University of California, San Diego, CA, USA

21. Department of Internal Medicine and Human Genetics , University of Michigan, Ann Arbor, MI, USA

22. The Institute for Translational Genomics and Population Sciences , Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA

23. Research Unit Molecular Epidemiology , Institute of Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany

24. Department of Diagnostic and Interventional Radiology , Faculty of Medicine, University of Freiburg, Freiburg, Germany

25. Department of Molecular Genetics , Erasmus University Medical Center, Rotterdam, The Netherlands

26. Department of Radiation Oncology , Erasmus University Medical Center, Rotterdam, The Netherlands

27. Department of Vascular Surgery , Erasmus University Medical Center, Rotterdam, The Netherlands

28. Laboratory of Experimental Cardiology , Division Heart and Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

29. Laboratory of Clinical Chemistry & Hematology , Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

30. Department of Gastroenterology and Hepatology , Erasmus University Medical Center, Rotterdam, the Netherlands

31. Department of Internal Medicine , Erasmus University Medical Center, Rotterdam, the Netherlands

32. Department of Medicine , Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA

33. School of Medicine , Stanford University, Stanford, CA, USA

34. Department of Surgery , Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

35. Corporal Michael J. Crescenz VA Medical Center , Philadelphia, PA, USA

36. Department of Epidemiology , University of Washington, Seattle, WA, USA

37. Department of Health Services , University of Washington, Seattle, WA, USA

38. Institute for Community Medicine , University Medicine Greifswald, Greifswald, Germany

39. Chair of Epidemiology , Institute for Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany

40. German Center for Diabetes Research , Neuherberg, Germany

41. Collaborative Health Studies Coordinating Center , Department of Biostatistics in the School of Public Health, University of Washington, Seattle, WA, USA

42. Institute of Genetic Epidemiology , Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany

43. Chair of Genetic Epidemiology , Institute for Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany

44. Institute of Medical Biostatistics , Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, Mainz, Germany

45. Institute of Human Genetics , Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany

46. Institute of Human Genetics , Technische Universität München, München, Germany

47. Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) , VA Boston Healthcare System, Boston, MA, USA

48. Department of Epidemiology and Biostatistics , Imperial College London, London, UK

49. MRC Centre for Environment and Health , School of Public Health, Imperial College London, London, UK

Abstract

Abstract Progressive dilation of the infrarenal aortic diameter is a consequence of the ageing process and is considered the main determinant of abdominal aortic aneurysm (AAA). We aimed to investigate the genetic and clinical determinants of abdominal aortic diameter (AAD). We conducted a meta-analysis of genome-wide association studies in 10 cohorts (n = 13 542) imputed to the 1000 Genome Project reference panel including 12 815 subjects in the discovery phase and 727 subjects [Partners Biobank cohort 1 (PBIO)] as replication. Maximum anterior–posterior diameter of the infrarenal aorta was used as AAD. We also included exome array data (n = 14 480) from seven epidemiologic studies. Single-variant and gene-based associations were done using SeqMeta package. A Mendelian randomization analysis was applied to investigate the causal effect of a number of clinical risk factors on AAD. In genome-wide association study (GWAS) on AAD, rs74448815 in the intronic region of LDLRAD4 reached genome-wide significance (beta = −0.02, SE = 0.004, P-value = 2.10 × 10−8). The association replicated in the PBIO1 cohort (P-value = 8.19 × 10−4). In exome-array single-variant analysis (P-value threshold = 9 × 10−7), the lowest P-value was found for rs239259 located in SLC22A20 (beta = 0.007, P-value = 1.2 × 10−5). In the gene-based analysis (P-value threshold = 1.85 × 10−6), PCSK5 showed an association with AAD (P-value = 8.03 × 10−7). Furthermore, in Mendelian randomization analyses, we found evidence for genetic association of pulse pressure (beta = −0.003, P-value = 0.02), triglycerides (beta = −0.16, P-value = 0.008) and height (beta = 0.03, P-value < 0.0001), known risk factors for AAA, consistent with a causal association with AAD. Our findings point to new biology as well as highlighting gene regions in mechanisms that have previously been implicated in the genetics of other vascular diseases.

Publisher

Oxford University Press (OUP)

Subject

Genetics (clinical),Genetics,Molecular Biology,General Medicine

Link

https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddac051/45186384/ddac051.pdf

Reference83 articles.

1. Abdominal aortic aneurysm: update on pathogenesis and medical treatments;Golledge;Nat. Rev. Cardiol.,2019

2. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases;Erbel;Eur. Heart J.,2014

3. The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm;Chaikof;J. Vasc. Surg.,2018

4. Cardiovascular risk in patients with small and medium abdominal aortic aneurysms, and no history of cardiovascular disease;Sohrabi;Br. J. Surg.,2014

5. Global and regional burden of aortic dissection and aneurysms: mortality trends in 21 world regions, 1990 to 2010;Sampson;Glob. Heart,2014

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